Recently, many non-steroidal anti-inflammatory analgesics for transdermal absorption have been formulated and widely used for various inflammatory diseases such as chronic rheumatism, osteoarthritis, spondylosis deformans, and low back pain. Especially, diclofenac sodium has an excellent anti-inflammatory analgesic action, and therefore, is widely used as an oral  agent or a suppository in clinical scenes. However, diclofenac sodium is also known to cause various side effects such as gastrointestinal disease.
In order to alleviate these side effects, an external preparation for transdermal absorption of diclofenac sodium has been investigated.
Especially, an external patch enables an efficient and continuous treatment because it can control a drug dosage and directly transfer a drug to the affected area just below the patch. However, diclofenac sodium has a very low solubility in water or an oily ingredient. Therefore, it is difficult to prepare a patch in which diclofenac sodium is completely dissolved, and even if such patch can be prepared by the addition of an excessive amount of an agent such as a diclofenac sodium solubilizer, it is difficult to preserve such patch with diclofenac sodium remaining in the dissolved state without a crystal precipitation in the patch for a long time. Also, when an oily ingredient which can highly dissolve diclofenac sodium is contained in an aqueous patch at a high concentration, the compatibility with other ingredients becomes worse, a phase separation readily occurs, and a stable storage for a long time becomes impossible. In addition, because the transdermal absorbability of diclofenac sodium is generally low, various investigations or efforts have been performed until now to solve these problems. However, a formulation which can solve the above problems has not been obtained so far.
For example, the following Patent Document 1 proposes a patch with an enhanced transdermal absorbability of diclofenac sodium prepared by adding crotamiton and a weak fatty acid to diclofenac sodium to convert the drug to a free acid. However, the stability of diclofenac sodium may be lowered by converting diclofenac sodium to the free acid, and further, the transdermal absorbability of the drug is not sufficiently high.
The following Patent Document 2 proposes a patch which has an excellent transdermal absorption efficiency of diclofenac sodium and a small chronological change consisting of two layers, i.e., an agent layer containing diclofenac sodium and a base layer not containing diclofenac sodium. However, because the preparation of this patch requires a process for pasting the agent layer and the base layer after they are separately prepared and spread, there are problems in complicated process management, economic efficiency, etc.
The following Patent Document 3 proposes an aqueous patch containing diclofenac sodium, an absorption enhancer consisting of 1-menthol and propylene glycol, and a hydrophilic base comprising a water-soluble polymer as the main ingredient. However, the solubility of diclofenac sodium in the patch is low and there is a fear of crystallization of the drug during a long storage, and further, the transdermal absorbability of the drug is not sufficiently high.
The following Patent Document 4 proposes the addition of 1-menthol and pyrrolidones (at least one of pyrrolidone or derivatives thereof) as transdermal absorption enhancers of diclofenac sodium. However, the solubility of diclofenac sodium in the aqueous patch is low and there is a fear of crystallization of the drug during a long storage, and further, the transdermal absorbability of the drug is not sufficiently high.                Patent Document 1: JP 07-089853 A        Patent Document 2: WO 2004/071499        Patent Document 3: JP 05-032544 A        Patent Document 4: JP 11-222443 A        